Etravirine

Medical uses

In the US, etravirine is indicated for the treatment of HIV-1 infection in treatment-experienced patients aged two years of age and older.

In the EU, etravirine, in combination with a boosted protease inhibitor and other antiretrovirals, is indicated for the treatment of human-immunodeficiency-virus-type-1 (HIV-1) infection in antiretroviral-treatment-experienced people aged six years of age and older.

Contraindication

People with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this etravine.

Adverse effects

In 2009, the FDA prescribing information for etravirine was modified to include "postmarketing reports of cases of Stevens–Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme, as well as hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver failure."

Mechanism of action

Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs, mutation K103N for efavirenz and Y181C for nevirapine. This potency appears to be related to etravirine's flexibility as a molecule. Etravirine is a diarylpyrimidine (DAPY), a type of organic molecule with some conformational isomerism that can bind the enzyme reverse transcriptase in multiple conformations, allowing for a more robust interaction between etravirine and the enzyme, even in the presence of mutations.

Chemistry

Etravine forms as colourless orthorhombic crystals in space group Pna21. The structures of these and of a number of solvate and salt forms have been reported.

Research

Etravine has been studied for use in a drug repositioning application. Etravirine was shown to cause an increase in frataxin production.

References

References

1. (15 August 2023). "Intelence- etravirine tablet".
2. (28 August 2008). "Intelence EPAR".
3. "Appendix A: Key to Acronyms". [[Department of Health and Human Services]].
4. (October 2007). "Antiviral drugs in the treatment of AIDS: what is in the pipeline ?". European Journal of Medical Research.
5. (18 January 2008 }}{{dead link). "FDA Approves HIV Drug Etravirine". [[Associated Press]].
6. (1 April 2008). "First New NNRTI in Nearly a Decade to Benefit Canadians with HIV/AIDS". Janssen-Ortho Inc..
7. "Intelence receives marketing authorisation in the European Union for HIV combination therapy". Tibotec.
8. "Etravirine (TMC125, ''Intelence'') granted accelerated approval in US". [[aidsmap]].
9. "Etravine: Summary of product characteristics". [[European Medicines Agency.
10. "FDA Medwatch Safety Information".
11. (15 January 2008). "Etravirine—Countdown to Launch". AIDSmeds.com.
12. (May 2004). "Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants". Journal of Medicinal Chemistry.
13. (7 August 2013). "New Solid Forms of the Anti-HIV Drug Etravirine: Salts, Cocrystals, and Solubility". Crystal Growth & Design.
14. (November 2021). "New solvates and a salt of the anti-HIV compound etravirine". Acta Crystallographica Section C: Structural Chemistry.
15. (March 2019). "Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia". Movement Disorders.